Project 003 - Project Summary/Abstract - Systems, Pathways & Targets (SPT) The Systems, Pathways & Targets (SPT) Program is a newly formed program (created in 2011) that integrates cancer-focused members from two prior programs with new members who have expertise in the systems biology of cancer. SPT members focus on cellular signaling, tissue morphogenesis and computational modeling/bioinformatics. The overarching goal of this program is to identify key proteins or points of crosstalk for therapeutic intervention. To achieve this goal, three aims are proposed: 1) Identify key targets in signaling pathways, developmental pathways, and metabolic programs that are relevant to cancer initiation, progression, and therapeutic resistance, 2) Develop multi-disciplinary teams to study tumor heterogeneity and microenvironment/cellular interactions, 3) Diversify multi-disciplinary approaches to develop new therapeutic strategies. SPT members include cell biologists, immunologists, geneticists, developmental biologists, computational scientists, and clinicians. Dr. David Fruman and Dr. John Lowengrub direct the program as co- leaders. Their expertise in cellular signaling and drug development (Fruman) and systems biology of the tumor microenvironment (Lowengrub) embody the scientific breadth of basic research in the program, their partnering with basic and physician scientist members demonstrates the collaborative nature of SPT. Since the last renewal, exciting progress has been made in the identification of new targets in cancer cells and the development of small lead compounds against those targets. The first subset of these molecules are making their way to the bedside in the form of pre-clinical tests and clinical trials. Strategic partnering with members of the Chemical and Structural Biology (CSB) program has led to the synthesis of a second subset of molecules for evaluation in pre-clinical assays. In addition, SPT members have collaborated with bioengineers in the Onco-Imaging and Biotechnology (OIB) program for the development of new tools for cancer research. New collaborations with members of the Cancer Prevention, Outcomes and Survivorship (CPOS) program show promise in identifying and addressing issues in the catchment area of the cancer center. In the future, the SPT program leadership will continue to leverage the unique breadth and synergy among its members to build collaborative teams that tackle long-standing problems using bold and innovative approaches. Membership: 55 Members from 17 Departments Funding: $2,731,793 NCI (Totals); $9,767,626 Other Peer-Reviewed (Totals) Publications: 588 Publications, 15% Inter-programmatic; 12% Intra-programmatic